Mass spectrometry is an analytical technique used to determine the molecular weight (or mass) of a sample or molecule (“analyte”) and is used in a wide variety of applications including trace gas analysis, pharmocokinetics, and protein characterization, to name a few. Mass spectrometry techniques typically include the ionizing of chemical compounds to generate charged molecules (“ions”) in order to separate them by the mass-to-charge (m/z) ratios. Accurate mass measurements and fragmentation technology determine for example elemental composition, sequence information, and quantitative (“amounts”) information. Ion mobility spectrometry measures the drift times of ions which is influenced by the size, (shape) and charge of the ions.
Various methods have been developed to ionize samples consisting of one or many molecules that are volatile and nonvolatile. For example, electrospray ionization (“ESI”) produces charged droplets of the solvent/analyte from a liquid stream passing through a capillary onto which a high electric field is applied relative to a counter electrode. The charged droplets are desolvated (evaporation of the solvent, but not the charge) until the Raleigh limit is reached in which the charge repulsion of like charges exceeds the surface tension of the liquid. Under these conditions so called “Taylor cones” are formed in which smaller droplets are expelled from the parent droplet and carry a higher ratio of charge to mass than the parent droplet. These prodigy droplets can undergo this same process until eventually ions are expelled from the droplet due to the high-repulsive field (ion evaporation mechanism) or the analyte ions remain after all the solvent evaporates.
Another ionization process called sonic spray ionization (“SSI”) has also been developed. In SSI, a high velocity of a nebulizing gas is used to produce charged droplets instead of an electric field as used in ESI.
However, these conventional methods of ionizing a solution with an analyte require an electric field or a high velocity gas, which increase the complexity and cost of the spectrometry system and lowers the throughput. The above methods also involve producing ions at or near atmospheric pressure and transferring them through a channel to a lower pressure for mass analysis, which is an inefficient process. The ions are multiply charged which extends the mass range of high performance mass spectrometers, improves IMS separations, and enhances intentional fragmentation such as collision induced dissociation (“CID”) and electron transfer dissociation (“ETD”), as examples, for structural characterization.
An example of an ionization method is matrix-assisted laser desorption/ionization (“MALDI”). In MALDI, a laser ablates analyte that is incorporated into a matrix (small molecule that absorbs radiation from the laser) which produces mostly singly-charged ions that are mass analyzed. More recently, an ionization method initially called laserspray ionization (“LSI”), currently laserspray ionization inlet (“LSII”) was discovered that produces ions of very similar charge states as ESI, but by laser ablation of a solid matrix/analyte mixture initiated from atmospheric pressure. This method is similar to MALDI in that a laser and a matrix are used, but does not require stringent absorption of the matrix at the laser wavelength. Ionization is initiated in the channel rather than by photoionization by the laser and produces multiply charged ions similar to those observed with ESI but from the solid state and surfaces. Other means can be used to ablate the matrix with analyte to enter into the channel, but a laser provides a high spatial resolution means of measurements. The laser-free version is referred to as matrix assisted ionization inlet (MAID. Common to MALDI and LSII is that location(s) of certain molecules can be imaged by their m/z from surfaces such as drugs from mouse brain tissue, as an example. When using a solid matrix, ionization is initiated in a heated channel depending on the small molecule matrix used. Using solutions, ionization is initiated in the channel upon heating the channel.